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• W2247286219 endingPage "82" @default.
• W2247286219 startingPage "71" @default.
• W2247286219 abstract "The cardiac electrical disorder long QT syndrome (LQTS) pre-disposes affected individuals to ventricular arrhythmias and sudden death. Dysfunction of the human ether-a-go-go-related gene (hERG)-encoded rapidly activating delayed rectifier K(+) channel (IKr) is a major cause of LQTS. The expression of hERG channels is controlled by anterograde trafficking of newly synthesized channels to and retrograde degradation of existing channels from the plasma membrane. We have previously shown that the E3 ubiquitin (Ub) ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2) targets the PY motif of hERG channels to initiate channel degradation. Although both immature and mature hERG channels contain the PY motif, Nedd4-2 selectively mediates the degradation of mature hERG channels. In the present study, we demonstrate that Nedd4-2 is directed to specific cellular compartments by the Nedd4 family interacting proteins, Nedd4 family-interacting protein 1 (Ndfip1) and Ndfip2. Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2. These findings extend our understanding of hERG channel regulation and provide information which may be useful for the rescue of impaired hERG function in LQTS." @default.
• W2247286219 created "2016-06-24" @default.
• W2247286219 creator A5011343099 @default.
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• W2247286219 date "2015-10-30" @default.
• W2247286219 modified "2023-10-03" @default.
• W2247286219 title "Regulation of the human ether-a-go-go-related gene (hERG) potassium channel by Nedd4 family interacting proteins (Ndfips)" @default.
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• W2247286219 doi "https://doi.org/10.1042/bj20141282" @default.
• W2247286219 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26363003" @default.
• W2247286219 hasPublicationYear "2015" @default.
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